Tuesday, September 28, 2010

About 18 months ago I went to Chartres for the filming of a documentary about the Gothic cathedrals for Nova. The documentary is now finished, and airs in October in the US. I’ve no idea how it ended up, but there is an outtake available here which bodes well. I’m glad they managed to find a use for this footage, since it wasn’t easy taking it: up in the galleries we had to keep persuading the organist to postpone his practice, while out on the front steps we had to placate the resident alcoholics and grab takes between rain squalls. I’d frozen my gonads off by the end of it. That, no doubt, is all very thirteenth-century.

Friday, September 24, 2010

Here’s the full-cream version of my Lab Report for Prospect in October.

The IPCC is in a bind. There are good arguments for reforming the way it operates, not least improving the efficiency and transparency of its review process. A recent independent assessment by the InterAcademy Council, representing all the world’s major science academies, agreed with that but concluded that the IPCC’s scientific conclusions are reliable and that it has generally worked well on a shoestring. But should its chair, Rajendra Pachauri, stay? Pachauri has been pilloried for errors that led to unjustified forecasts about melting of the Himalayan glaciers – a bad mistake, but negligible in the grand scheme. He has also been unjustly smeared over alleged conflicts of interest. There is nothing here to warrant resignation

But Pachauri’s leadership during the IPCC’s tribulations of the past year has not been inspiring, and more to the point, all leaders grow stale eventually. A change could bring fresh vigour and restore public confidence. Yet such is the aura of distrust fomented by the smear campaign that it would now be all but impossible for Pachauri to step down without being seen to validate climate sceptics’ criticisms. We are now in a mirror-image reality in which some consider Bjorn Lomborg’s U-turn on the threat of climate change more principled than Pachauri’s steadfast advocacy of the science. A reformed IPCC would be welcome, but there will be no winners.

Although it’s perhaps no surprise that the restoration of federal funding for stem-cell research in the United States under the Obama administration is not plain sailing, no one could have foreseen the oddness of the latest, potentially devastating obstacle. The injunction issued by a district court judge in Columbia against such funding stems from a case brought not by Christian ‘pro-life’ groups, who object to the destruction of human embryos in harvesting new stem-cell lines, but by two stem-cell scientists. James Sherley and Theresa Deisher work on adult stem cells and oppose research on embryonic cells, saying that the adult-cell work is both scientifically and ethically superior.

Outsiders to the US legal system will be baffled that a district judge can, by reinterpreting the meaning of a long-standing constraint on embryonic stem-cell work, force the National Institutes of Health instantly to freeze all funding, plunging work in progress into limbo and ensuring funding chaos months or years down the line. But there it is: Chief Judge Royce Lamberth has decided that the 1996 Dickey-Wicker Amendment to NIH budget legislation, prohibiting funding for research involving the creation and destruction of embryos, in fact must prohibit all embryonic stem-cell work whether or not it destroys or creates embryos. The injunction has been appealed by the US Department of Justice.

The amendment itself is probably here to stay, since it impinges also on abortion, but the current Obama policy had left room for the use, with donor consent, of embryos from fertility clinics that would otherwise be destroyed.

Sherley is a complicated character with an agenda that is hard to read. But the fact that a maverick case in a district court can wreck an entire nation’s research effort at the forefront of medical science is chilling.

Because every month now seems to bring a new complete genome sequence – now mouse-ear cress, now the panda – it might have been tempting at first to greet the announcement of the wheat genome with a touch of ennui. But no longer. Drought and flood have devastated wheat yields in Russia and China. Russia, one of the world’s biggest producers, has now imposed an export ban that has sent wheat prices soaring, threatening the food security of millions of people. The riots in Mozambique over bread prices may be just a taste of what is to come.

This is why the wheat genome sequence is one of the most important so far, and why public access to the data granted by the researchers, led by a team at Liverpool University, is so valuable and commendable. The genetic information should point to shortcuts for breeding of new, hardier varieties, as well as identifying specific genes that might be engineered to improve resistance to drought and disease.

Why, then, has wheat not been genetically sequenced sooner? The answer is sobering: the genome is not only larger than that of most crops, but is five times larger than the human genome. And some scientists have cautioned that the British work offers just a preliminary first draft: the International Wheat Genome Sequence Consortium says that there is still a lot of work to be done in sorting and ordering the raw data.

The much-vaunted medical benefits of sequencing the human genome itself have just received some vindication from the results of clinical trials of the anti-cancer drug PLX4032. The dramatic potential of the drug for shrinking skin-cancer tumours was reported in August, and is confirmed by a recent paper in Nature. But the real excitement stems from the approach: the drug was developed to target a specific carcinogenic mutation of a gene called BRAF, involved in cell growth. The problem is that there are several dangerous mutations of BRAF alone, and thousands of other genetic mutations that also cause cancer. But the new results show that targeting a particular mutation can be highly effective, hitting only those cancer cells that possess it instead of employing the scattershot attack of current cancer chemotherapies. If many mutant-specific drugs come online, rapid gene profiling of patients could enable them to be given precisely the right treatment, without the debilitating side-effects. That, however, will require the development of an awful lot of new drugs. [See my Prospect article on the problems with Big Pharma.]

Friday, September 17, 2010

My review of Hawking’s new book has now been published, although you’re unlikely to stumble across it unless you live in Abu Dhabi. Since it is published pretty much verbatim, and seems to be freely accessible, I won’t post it again here.

Friday, September 10, 2010

I have acommenton the Prospect blog about the way the media has been hyperventilating (seehereandhere(Graham Farmelo being characteristically astute) andhere) about Stephen Hawking. Here is how it started out. [Incidentally, I can't figure out why my last paragraphs are reverting to Roman typeface. Sorry for this distraction.]

It’s a harsh reality of journalistic life that you will sometimes have to write up ‘news’ that is neither new nor significant, simply because your editor knows that everyone else will do so. That is the generous interpretation of the blanket media coverage of Stephen Hawking’s pronouncement that God is no longer needed to create the universe.

Hawking has form in this arena, having previously been accorded oracular status when he uttered some comment about a Theory of Everything permitting us to ‘know the Mind of God’, the kind of idle metaphor that only someone lacking any serious interest in the interface of science and religion would employ. Hawking clearly had not read Francis Bacon’s Advancement of Learning, which wisely declares that ‘if any man think, by his inquiries after material things, to discover the nature or will of God, he is indeed spoiled by vain philosophy.’ Although interpretations of Bacon’s pieties as those of a closet atheist minding his back are unlikely, he did at least have the good taste thus to dispense with God at the outset.

Let’s not be too harsh on Hawking: the man is one of the best physicists in the world. The problem is that, in the public view, this statement probably seems as absurd as saying that Messi is a good striker: a lame way of acknowledging incomparable genius. Most people will be astonished to hear that Hawking is not rated by his peers among the top ten physicists even of the 20th century, let alone of all time. They probably imagine he has so far been denied a Nobel prize out of sheer jealousy. Hawking is extremely smart, but so are others, and he is a long way from being Einstein’s successor.

More importantly, Hawking has no reputation among scientists as a deep thinker. There is nothing especially profound in what he has said to date about the social and philosophical implications of science in general and cosmology in particular. There is far more wisdom in the views of Martin Rees, John Barrow or Phil Anderson, not to mention the old favourites Einstein, Bohr and Feynman. Hawking’s latest remarks on the redundancy of God have little depth, as Paul Davies showed easily enough in the Guardian: if you have any kind of law-like regularity in the universe, the door is always open for those who like to attribute it to God. And Mary Warnock (no religious apologist) points out – or reminds us that Hume pointed out – that the Biblical God is not simply or even primarily a God who made the universe. It’s a sterile debate, as Bacon already saw.

This makes it ridiculous, then, that Hawking’s announcement in his new book The Grand Design (I’m currently reviewing this, and will post the review shortly) has been greeted as though it is the final judgement of science on the Biblical Creation: Hawking Has Spoken. Even atheists must feel some sympathy for the likes of Rowan Williams having to comment on such a shallow assertion, as though Hawking is supposed to have set the foundations of their faith quaking. Hawking is speaking about the God of Boyle and Newton, not the God of contemporary theology. (This is not to deny that millions still believe in this anachronistic, childish vision of God, who waved his fingers and made the world, but just to say that it is a bit silly to pander to it.)

So why does Hawking get awarded this status by the idolatory press? It’s time to stop being squeamish and take the bull by the horns. The Cult of Hawking is the Cult of the Great Mind in the Useless Body. It is attributable in part to a simple, ghoulish fascination with the man’s physical disability, but more so (and more troublingly) to the unspoken astonishment that a man with such severe bodily impairment can be intelligent. It speaks volumes about our persistent prejudices about disability.

I find it disturbing that the media plays along with this so readily, even while now seemingly keen to feign blindness to Hawking’s condition. It is hard to know whether Hawking recognizes this situation himself. He has always seemed inspiringly stoical, even gently self-mocking, in the face of the extreme challenges of his affliction. If he knows that his fame and reputation stem from his illness, no one has any right to expect him to comment on it. But as for the rest of us: the more we turn Hawking into a guru, the more we do a disservice to everyone else whose minds are vibrant while their bodies are impaired.

Tuesday, September 07, 2010

You want to be happy? Here’s how: be highly educated, female, wealthy, not middle-aged (tell me about it), married and self-employed. These are among the most salient characteristics of people who describe themselves as being the most happy. Misery, meanwhile, comes from unemployment, low income, divorce and poor health.

Not rocket science, is it? Nevertheless, the booming discipline of ‘happiness studies’ continues to excite controversy. What is cause and effect, for example? Are people happier when they marry, or do happy people marry?

And what exactly do we mean by happiness: that we laugh a lot, feel optimistic and secure in our lives, are serenely calm or deliriously hedonistic? In a recent Gallup poll of national happiness, the USA came fifth, and yet at the same time came 89th from ‘best’ (out of 151) in terms of ‘worry’ and had the fifth highest stress levels. How to make sense of that? Does happiness compensate for stress, or are they ineluctably conjoined?

Besides, is happiness a desirable goal? That might seem obvious (it was to the authors of the US Declaration of Independence) – and it surely seems a better measure of human wealth than conventional ‘well-being’ economic indices such as GDP. But what if a happy nation is a selfish or profligate one? And who’s to say that the inhabitants of Aldous Huxley’s Brave New World would not, blissed out by the drug soma, have rated high on the happiness scale?

These dilemmas have deep roots. Jeremy Bentham’s utilitarian political philosophy in the nineteenth century sought to arrange for the maximum happiness for the greatest number of people, according to a so-called ‘hedonistic calculus’: a principle, however, rendered indeterminate by what has been called the ‘fallacy of double optima’, with no unique optimum.

One of the most contested issues is the relationship between happiness and income. Everyone agrees that abject poverty is miserable, but how does the relationship play out above that unfortunate state? While being female or married are all-or-nothing factors, income is quantitative: if being wealthy makes you happy, does being more wealthy make you more happy?

Since most of us are, by definition, not relatively wealthy in our society, we probably feel a glow of self-righteous satisfaction from studies suggesting there is a ‘wealth threshold’ above which happiness no longer increases [1][2]. That fits with intuition: the super-rich do not strike us as a particularly joyful bunch. (In the UK we like to wheel on the Royal Family as the prime exhibit, disregarding the fact that less representative members of society you will never find.)

But now Nobel laureate economist Daniel Kahneman and his colleague Angus Deaton at Princeton University have thrown a cat among the pigeons. In a new paper in The Proceedings of the National Academy of Sciences USA [3] they use the US data from the recent Gallup survey to argue that income does continue to impact on our evaluation of life satisfaction as we enter the realm of the rich.

Does this validate the anonymous quip that those who say money can’t buy happiness don’t know where to shop? Not exactly. Kahneman and Deaton say that previous discussions have been muddied by a failure to distinguish a sense of emotional well-being from our life evaluation. The first refers to daily experience: how much we laugh, how relaxed we feel as we go about our life. The second is a more objective overview: are we content with our family, job, house, insurance, credit rating? It is not hard to imagine the head of a big corporation feeling good about all this while never cracking a grin.

The Gallup poll surveyed more than 700,000 US residents, although Kahneman and Deaton jettison about a quarter of the responses because they appear unreliable. From the rest, they deduce that income is more closely correlated with life evaluation than with emotional well-being, and that this correlation persists for all income levels, at least up to around $160,000 per annum. While reported well-being also generally increases with income, this relationship plateaus at an income of around $75,000.

For all their ambiguities, happiness studies are closely monitored by politicians and policy makers, not least because policies that make people happy seem likely to win votes. What will they make of these findings? Is it better to promote good life evaluation, or emotional well-being?

Kahneman and Deaton refrain from taking a position – and the richness and subtlety of their data advise against glib answers. As they imply, any society should wish to improve the lot of people who have poor emotional health and are gloomy about their prospect. But their results, while complicating the previous picture, surely suggest that income (and dare one therefore add, taxation levels?) should not be regarded as a relevant happiness dial for the comfortably off. While some might be determined to extract the conclusion that, as the New York Times once put it [4], ‘maybe money does buy happiness after all’, there is a strong case here that better education, secure health provision, lowering of stress, and the nurturing of social and familial relationships offer a far greater dividend of smiles.

Wednesday, September 01, 2010

Bit of overmatter from my Prospect Lab Report this month, as the top story below blew up shortly before it went to press, so the last two stories below were shelved. Here, as ever, is the unexpurgated version.

It would be nice to be able to report that the much trumpeted ‘end of antibiotics’ is just a slice of media alarmism. But it isn’t. The danger that just about all our existing antibiotics will soon be powerless against resistant bacteria, as claimed in Lancet Infectious Diseases, is all too real. A paper in the journal reports the emergence and spread of strains of common pathogens, such as E. coli and the pneumonia bug K. pneumoniae, containing a gene that confers resistance against even current last-resort antibiotics called carbapenems. Such bacteria, Chris Walsh of Harvard Medical School confirms, “are on the brink of being impossible to treat with existing antibiotics.” “This is a very serious problem”, agrees Gerry Wright, a specialist in antibiotic resistance and discovery at McMaster University in Ontario. Without antibiotics, even routine surgery could cause fatal infections.

Antibiotic resistance has been with us ever since penicillin revolutionized medicine. So why the problem now? Partly, it’s simply becoming harder to find new drugs to expand the arsenal. But the difficulties also stem from practices within the pharmaceutical industry. “This is a very grim time in antibacterial drug development”, says Wright. “The reasons are complex, but the fact that many pharmaceutical companies have moved to a focus on chronic diseases is one.”

Wright is one of several specialists who have been clamouring for years about the danger. In 2004, Carl Nathan of Cornell University’s Weill Medical College decried the way companies look for profitable blockbuster antibiotics. These are general-purpose drugs for chronic infections, and their widespread use quickly elicits resistance. But if their use is restrained, profits fall and funding and expertise leaches away. This, along with regulatory hurdles, the debilitating effects of a spate of big pharma mergers, and myopic focus on hitting tried-and-tested biochemical targets in the pathogens, has now almost dried up the antibiotic development pipeline. Nathan called for an overhaul in the way new antibiotics are sought and brought to market, including a vigorous not-for-profit pharmaceutical sector.

Something certainly needs to change: this is a global problem for which the market may not offer any solution. “Multidrug resistant bacteria will only continue to spread”, says Wright. “There is no chance that the problem will go away.”

*****

The UK coalition government’s plan to dismantle the Human Fertility and Embryology Authority in its cull of ‘health quangos’ is nothing short of vandalism.

The Health Protection Agency, also on the hit list, supplies vital advice about infectious diseases to the government, public and medical profession. But that demands rather specific expertise which could at least conceivably be transferred intact within the civil service. The HFEA is different.

Set up in 1991 after much governmental procrastination in the wake of the first IVF birth (1978) and the subsequent Warnock Report (1984) on embryo research, its responsibilities ballooned as developments in embryology and assisted conception accelerated. The authority’s recent wrestling with the ethics of human-animal hybrid embryos and stem-cell research seems a long way from treatments for infertility, but there is an inextricable link between them, historically and scientifically. This is one reason why the possible plan floated by Health Secretary Andrew Lansley to parcel out the HFEA’s work to three other bodies is naïve and potentially dangerous. Decisions about these delicate matters at the forefront of reproductive and biomedical technology require a comprehensive overview of the context, and ever more so as time goes by.

The real tragedy is that the HFEA did its job so well, as attested by the fact that it managed to upset both religious (and secular) conservatives, for perceived liberalism, and scientists, for alleged restrictiveness (despite the UK having one of the most permissive embryo research frameworks in the world). The HFEA was genuinely independent, refusing to kowtow to government, scientists, IVF clinics, religious groups, or public opinion. Doubtless some of its decisions could be criticized, but they were always taken with sober, informed consideration. It was a bulwark against the hazards of both a laissez-faire free market in infertility treatment and knee-jerk reactionary prohibition. It will be a miracle if the same acumen can be assembled from the scattered remains.

*****

The announcement of an antiviral vaginal gel that can reduce HIV infection by around 50 percent is good news, however qualified. The current clinical trial, conducted by the Durban-based Centre for the AIDS Program of Research in South Africa, is modest in scale and awaits replication, along with more data on safety and a better understanding of why it doesn’t always succeed. But the great virtue of this strategy is that it gives some autonomy to women, who can reduce their chance of contracting the virus when male sexual partners refuse to use a condom. In South Africa, a third of all women between 20 and 34 are thought to be HIV-positive, and they account for around 60% of all new infections.

The gel contains an antiviral drug which interferes with a key enzyme involved in viral replication, unlike previous efforts which have sought either to inhibit the entry of viruses into cells or to kill the viruses (or infected cells) directly. Testing on 889 HIV-negative women over two years showed that regular use could reduce the chance of infection by 54%. The gel should be very cheap per dose and has few side-effects. The question now is how to balance the urgency of need against time-consuming confirmation and in-depth clinical testing.

There was more promising news with the announcement that two ‘therapeutic vaccines’ for HIV – which aim to prevent transmission from infected people rather than preventing infection in the first place – have at last shown some success in boosting immune systems debilitated by HIV. The vaccines use pieces of RNA from the virus to stimulate an immune response.

Many AIDS researchers had concluded that therapeutic vaccines would not work, and even now the response to the new trials, which report only a modest suppression of the virus, is somewhat muted. Some fear the strategy might backfire by boosting evasive viral mutations.

*****

It’s a good time to be an oil specialist: lucrative contracts beckon both from BP and from the US government as they prepare for the obligatory Natural Resource Damage Assessment. But there are strings attached in either case: you probably won’t be able to publish your research for confidentiality reasons. Some academics have already declined offers for this reason. There is of course nothing very usual about gag rules for work contracted by a private company or for government-backed research with legal implications. But it could mean that, in the absence of significant independent funding for such research, a detailed understanding of the effects of the Deepwater Horizon spill will never be made public.

On the other hand, oil clean-up technology could be improved by the carrot of a $1.4 million prize dangled by the X Prize Foundation, a Californian organization that aims to stimulate “radical breakthroughs for the benefit of humanity”. The company has previously offered a $10 million award for the development of a privately funded, manned spacecraft, which was claimed by the company Scaled Composites now working on Richard Branson’s Virgin Galactic commercial spaceflight programme. Entries for the oil prize are already being prepared. It’s good that the Foundation has noticed there are better ways to spend its money.